Cecilie N Lydholm1, Ole Köhler-Forsberg2, Merete Nordentoft3, Robert H Yolken4, Preben B Mortensen5, Liselotte Petersen5, Michael E Benros6. 1. Mental Health Centre Copenhagen, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus University Hospital, Risskov, Denmark. Electronic address: rwt596@alumni.ku.dk. 2. Mental Health Centre Copenhagen, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus University Hospital, Risskov, Denmark; Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. 3. Mental Health Centre Copenhagen, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus University Hospital, Risskov, Denmark. 4. Stanley Division of Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland. 5. iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus University Hospital, Risskov, Denmark; National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark. 6. Mental Health Centre Copenhagen, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus University Hospital, Risskov, Denmark; National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark.
Abstract
BACKGROUND: Previous studies have shown associations between maternal infections during pregnancy and increased risks of schizophrenia and autism spectrum disorder in the offspring. However, large-scale studies investigating an association between parental infections both during and outside the pregnancy period and the risk of any mental disorder in the child are lacking. METHODS: A nationwide Danish cohort study identified 1,206,600 children born between 1996 and 2015 and followed them to a maximum of 20 years of age. Exposure included all maternal and paternal infections treated with anti-infective agents or hospital contacts before, during, or after pregnancy. The main outcome was a diagnosis of any mental disorder in the child. Hazard ratios (HRs) were calculated using Cox regression analysis. RESULTS: Maternal infections during pregnancy treated with anti-infective agents (n = 567,016) increased the risk of mental disorders (n = 70,037) in the offspring (HR, 1.09; 95% confidence interval [CI], 1.06-1.12), which was more elevated (p < .001) than after paternal infections (n = 350,835; HR, 1.01; 95% CI, 0.98-1.03). Maternal hospital contacts for infections (n = 39,753) conferred an increased HR of 1.21 (95% CI, 1.14-1.28), which was not significantly (p = .08) different from the risk after paternal infections (n = 8559; HR, 1.07; 95% CI, 0.95-1.20). The increased risks observed during pregnancy were not different from the similarly increased risks for maternal and paternal infections before and after pregnancy. The risk of mental disorders increased in a dose-response relationship with the number of maternal infections treated with anti-infective agents, particularly during and after pregnancy (both p < .001). CONCLUSIONS: Maternal infections were associated with an increased risk of mental disorder in the offspring; however, there were similar estimates during and outside the pregnancy period.
BACKGROUND: Previous studies have shown associations between maternal infections during pregnancy and increased risks of schizophrenia and autism spectrum disorder in the offspring. However, large-scale studies investigating an association between parental infections both during and outside the pregnancy period and the risk of any mental disorder in the child are lacking. METHODS: A nationwide Danish cohort study identified 1,206,600 children born between 1996 and 2015 and followed them to a maximum of 20 years of age. Exposure included all maternal and paternal infections treated with anti-infective agents or hospital contacts before, during, or after pregnancy. The main outcome was a diagnosis of any mental disorder in the child. Hazard ratios (HRs) were calculated using Cox regression analysis. RESULTS:Maternal infections during pregnancy treated with anti-infective agents (n = 567,016) increased the risk of mental disorders (n = 70,037) in the offspring (HR, 1.09; 95% confidence interval [CI], 1.06-1.12), which was more elevated (p < .001) than after paternal infections (n = 350,835; HR, 1.01; 95% CI, 0.98-1.03). Maternal hospital contacts for infections (n = 39,753) conferred an increased HR of 1.21 (95% CI, 1.14-1.28), which was not significantly (p = .08) different from the risk after paternal infections (n = 8559; HR, 1.07; 95% CI, 0.95-1.20). The increased risks observed during pregnancy were not different from the similarly increased risks for maternal and paternal infections before and after pregnancy. The risk of mental disorders increased in a dose-response relationship with the number of maternal infections treated with anti-infective agents, particularly during and after pregnancy (both p < .001). CONCLUSIONS:Maternal infections were associated with an increased risk of mental disorder in the offspring; however, there were similar estimates during and outside the pregnancy period.
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